Clinical benefit of left atrial appendage closure in octogenarians

OBJECTIVESWhether left atrial appendage closure (LAAC) in octogenarians yield similar net clinical benefit compared to younger patients, was the purpose of the present study.METHODSTwo real-world LAAC registries, enrolling 744 consecutive Amplatzer and Watchman patients from 2009 to 2018, were retrospectively analyzed.RESULTSAll events are reported per 100 patient-years. Two hundred and sixty one octogenarians and 483 non-octogenarians with a mean follow-up of 1.7 ± 1.3 and 2.3 ± 1.6 years, and a total of 1,502 patient-years were included. Octogenarians had a higher risk for stroke (CHA₂DS₂-VASc score: 5.2 ± 1.2 vs. 4.3 ± 1.7, P < 0.0001) and bleeding (HAS-BLED score: 3.3 ± 0.8 vs. 3.1 ± 1.1, P = 0.001). The combined safety endpoint of major periprocedural complications and major bleeding events at follow-up was comparable (30/446, 6.7% vs. 47/1056, 4.4%; hazard ratio [HR] = 1.2; 95% confidence interval [CI]: 0.73−1.98;P = 0.48) between the groups. The efficacy endpoint of all-cause stroke, systemic embolism, and cardiovascular/unexplained death occurred more often in octogenarians (61/446, 13.7% vs. 80/1056, 7.6%; HR = 7.0; 95% CI: 4.53−10.93;P < 0.0001). Overall, octogenarians had a lower net clinical benefit, i.e., the composite of all above mentioned hazards, from LAAC compared to younger patients (82/446, 18.4% vs. 116/1056, 11.0%; HR = 4.6; 95% CI: 3.11−7.0;P < 0.0001). Compared to the anticipated stroke rate, the observed rate decreased by 41% in octogenarians and 53% in non-octogenarians. The observed bleeding rate was reduced by 10% octogenarians and 41% non-octogenarians. CONCLUSIONSLAAC can be performed with similar safety in octogenarians as compared to younger patients. On the long-term, it both reduces stroke and bleeding events, although to a lesser extent than in non-octogenarians.

As the most frequent arrhythmia, atrial fibrillation (AF) is associated with an increased risk of cognitive decline, stroke, disability, and mortality. The prevalence of AF is 2% in the general population and roses steadily with age, 3.7%−4.2% of subjects are aged above 60 years and up to 17% are octogenarians (age ≥ 80 years).^[1] Stroke risk from AF increases exponentially with age and is estimated at 23.9% per year in patients aged 80 years and older.^[2] Additionally, patients ≥ 80 years with AF, who are treated with oral anticoagulation (OAC), have a higher incidence of hemorrhagic events than younger patients.^[3] Therefore, octogenarians with AF are at highest risk for both thromboembolic and bleeding events. OAC is the standard of care for stroke risk. However, clinical evidence shows underuse of OAC in the elderly, who would have the highest benefit regarding ischemic stroke risk. This is mainly due to concerns about bleeding or prior bleedings. Factors of comorbidity, like impaired cognition, nonadherence, history of falls or bleedings, renal dysfunction, as well as concomitant drugs are reasons for leaving a substantial fraction of patients without stroke protection by OAC.^[4] Left atrial appendage closure (LAAC) is recommended as an alternative strategy for stroke prevention in AF patients who are not suitable for long-term treatment with OAC.^[5,6] Therefore, LAAC might be an attractive option for elderly AF patients. Several studies reported similar feasibility and safety of LAAC in subjects aged > 75 years compared to younger patients. ^[7–11] Furthermore, those studies showed favorable early clinical outcomes with regard to stroke and bleeding protection. Whether elderly patients have persistent long-term effects of LAAC has not been studied yet. Therefore, the subject of the present study was to compare the clinical benefit of LAAC in octogenarians with non-octogenarians based on the results of two real-world registries.     

改良阴茎成形术治疗青少年男性常见外生殖器畸形的疗效分析

目的:分析探讨2种改良阴茎成形术治疗青少年男性常见外生殖器畸形的临床效果。方法:选取2018年1月至2020年3月在南京医科大学附属常州第二人民医院接受改良阴茎成形术治疗的77例青少年男性外生殖器畸形患者,其中包皮过长及包茎患者56例,年龄（17.8±2.3）岁;隐匿阴茎患者21例,年龄（14.6±2.6）岁。回顾手术...     

Rap2B promotes cell adhesion,proliferation, migration and invasion of human glioma

Journal of Neuro-Oncology - Rap2B, a member of the GTP-binding proteins, is generally up-regulated in numerous types of tumors. Nevertheless, the influence and regulatory mechanisms of Rap2B in...     

Preliminary study on clinicopathological features of renal mucinous tubular and spindle cell carcinoma北大核心CSCD

Objective: To explore the clinicopathological features and prognosis of mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney in order to improve the understanding of the tumor. Methods: The clinical and pathological information of 15 patients with MTSCC in 7 hospitals were retrospectively collected and analyzed from July 2010 to July 2018. The sections were reviewed by two high-seniority pathologists. The EnVision two-step immunohistochemical staining technique was used to detect the expressions of villin, cytokeratin 7 (CK7), epithelial membrane antigen (EMA), alpha-methylacyl-CoA racemase (AMACR), transducin-like enhancer of split 1 (TLE1), hepatocyte nuclear factor-1p (HNF-1p)and kidney specific calcium binding protein (Ksp-cadherin). The fluorescence in situ hybridization (FISH) was used to detect the synovial sarcoma translocation (SYT)-synovial sarcoma X chromosome breakpoint (SSX) fusion gene in the patients with sarcomatoid changes and positive immunohistochemical staining of TLE1. Finally, the prognostic data of all patients and the relevant literature were reviewed. Results: Among 15 patients with MTSCC, seven of the patients were male and the other eight were female, with an average age of 62 years (ranging from 48 to 75 years). The tumors were found by chance in 12 patients during physical examination, and the other 3 patients developed clinical symptoms such as frequent urine pain or hematuria, including 1 patient with a history of renal calculi for 15 years. The cut surface of tumor is firm and grey or yellow. Except for 2 cases, the majority of tumors were well-circumscribed. Microscopically, 1 case showed neoplastic necrosis, 13 cases showed a mixture of mucinous stroma, tubules and spindle cells, 1 case was mainly composed of spindle cells and mucus, and 1 case was mainly composed of tubule and mucus. Some tumors were with obvious clear cytoplasmic changes, and two cases were accompanied by sarcomatoid differentiation. The immunohistochemical results showed that the positive rates of villin, CK7, EMA, AMACR, TLE1, HNF-1 p and Ksp-cadherin were 20.0% (3/15), 80.0% (12/15), 93.3% (14/15), 80.0% (12/15), 20.0% (3/15), 20.0% (3/15), 93.3% (14/15) and 13.3% (2/15), respectively; the result of FISH excluded synovial sarcoma. Eight patients were followed up wihout other treatment after operation. Bone metastasis occurred in half a year after operation in one patient with follow-up information, while no evidence of local recurrence or distant metastases was identified in the other 7 patients until now. Conclusion: A few cases of MTSCC can metastasize and belong to malignant tumors. The positive expressions of AMACR, CK7 and villin in some cases suggests that the tumor has both proximal and distal renal tubular origins. The positive expression of HNF-ip is correlated with the histological characteristics of MTSCC clear cytoplasm. © 2019 by TUMOR. All rights reserved.     

膝关节骨性关节炎推拿手法的力学特征和上肢核心肌群的疲劳研究

探讨膝关节骨性关节炎推拿手法的生物力学特征和生理学(表面肌电)特征,定量分析推拿手法的力学指标,建立一种客观评价推拿医生上肢核心肌群的疲劳状况的方法。招募10位推拿科医生,实时采集推拿医生拇指垂直压力和上肢表面肌电信号,研究垂直强度、次做功期与主做功期的时间比;研究操作该推拿手法时的上肢核心肌群;研究核心肌群的疲劳状况。结果表明,该推拿手法1 min内按压4次,平均垂直强度为(228±13)N,主做功期持续时间为(4.83±0.88)s,次做功期持续时间为(11.43±1.94)s,有效做功时间比为2.37±0.63。由上肢各肌肉群的平均积分肌电值(iEMG)和贡献率的降序可知,手法涉及上肢的核心肌群为拇短展肌(8.32±0.29,21.65%)、尺侧腕屈肌(5.67±0.32,14.74%)、肱三头肌(4.79±0.36,12.46%)、桡侧腕屈肌(4.60±0.12,11.96%)。在4 min的推拿过程中,拇短展肌的平均中值频率(MF)和平均功率频率(MPF)的下降程度是最大的,分别为30%和22%,即拇短展肌更易发生疲劳。因此,所研究的膝关节骨性关节炎推拿手法的生物力学特征和生理学(表面肌电)特征,为后续的人因工程研究和研制可替代推拿医生手法的自动化装置奠定良好的基础。     

The cost of Alzheimer's disease in China and re-estimation of costs worldwide

Introduction

The socioeconomic costs of Alzheimer's disease (AD) in China and its impact on global economic burden remain uncertain.

Neuroprotection of Exendin-4 by Enhanced Autophagy in a Parkinsonian Rat Model of α-Synucleinopathy

Glucagon-like peptide-1 (GLP-1) receptor stimulation ameliorates parkinsonian motor and non-motor deficits in both experimental animals and patients; however, the disease-modifying mechanisms of GLP-1 receptor activation have remained unknown. The present study investigated whether exendin-4 (a GLP-1 analogue) can rescue motor deficits and exert disease-modifying effects in a parkinsonian rat model of α-synucleinopathy. This model was established by unilaterally injecting AAV-9-A53T-α-synuclein into the right substantia nigra pars compacta, followed by 4 or 8 weeks of twice-daily intraperitoneal injections of exendin-4 (5 μg/kg/day) starting at 2 weeks after AAV-9-A53T-α-synuclein injections. Positron emission tomography/computed tomography (PET/CT) scanning and immunostaining established that treatment with exendin-4 attenuated tyrosine-hydroxylase-positive neuronal loss and terminal denervation and mitigated the decrease in expression of vesicular monoamine transporter 2 within the nigrostriatal dopaminergic systems of rats injected with AAV-9-A53T-α-synuclein. It also mitigated the parkinsonian motor deficits assessed in behavioral tests. Furthermore, through both in vivo and in vitro models of Parkinson’s disease, we showed that exendin-4 promoted autophagy and mediated degradation of pathological α-synuclein, the effects of which were counteracted by 3-methyladenine or chloroquine, the autophagic inhibitors. Additionally, exendin-4 attenuated dysregulation of the PI3K/Akt/mTOR pathway in rats injected with AAV-9-A53T-α-synuclein. Taken together, our results demonstrate that exendin-4 treatment relieved behavioral deficits, dopaminergic degeneration, and pathological α-synuclein aggregation in a parkinsonian rat model of α-synucleinopathy and that these effects were mediated by enhanced autophagy via inhibiting the PI3K/Akt/mTOR pathway. In light of the safety and tolerance of exendin-4 administration, our results suggest that exendin-4 may represent a promising disease-modifying treatment for Parkinson’s disease.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-021-01018-5.